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An outbreak of foodborne botulism in Taiwan
ARTICLE IN PRESS
Int. J. Hyg. Environ. Health 212 (2009) 82–86 www.elsevier.de/ijheh
An outbreak of foodborne botulism in Taiwan Chun-Kai Tsenga, Chon-Haw Tsaib, Chun-Hung Tsengb, Yu-Chi Tsenga, Fang-Yi Leec, Wei-Shih Huangb, a
Department of Emergency Medicine, China Medical University Hospital, Taichung, Taiwan Department of Neurology, China Medical University Hospital, Taichung, Taiwan c Department of Pathology, Taichung Veterans General Hospital, Taichung, Taiwan b
Received 6 June 2007; received in revised form 2 January 2008; accepted 23 January 2008
Abstract Botulism is a rare but serious paralytic disease caused by botulinum toxin. We report an outbreak of type B botulism in Taiwan in 2006. There were five cases involved in this outbreak. They present ileus and acute cranial nerve dysfunction including dysphagia and blurred vision. One of them had severe neurologic impairment and required mechanical ventilatory support. No patient received antitoxin administration because of delayed diagnosis. The food specimen revealed positive botulism toxin B. There were no fatalities. Consumption of fermented food was significantly associated with this outbreak. We also reviewed the characteristics of cases with botulism in Taiwan since 1985. r 2008 Elsevier GmbH. All rights reserved. Keywords: Antitoxin; Clostridium botulinum; Foodborne botulism; Type B
Introduction Clostridium botulinum is an anaerobic, gram-positive, spore-forming bacillus which exists in soil worldwide (Lund, 1990). It produces neurotoxins which bind to the pre-synaptic nerve endings of peripheral cholinergic nerves after entering the vascular system. The binding between botulinum toxin and peripheral cholinergic nerve endings blocks the release of acetylcholine which induces weakness of the innervating muscles. Associated symptoms include neurological, autonomic and gastrointestinal symptoms (Mackle et al., 2001). The initial Corresponding author. Tel.: +886 4 2052121x3681; fax: +886 4 22033474. E-mail addresses: [email protected], [email protected] (W.-S. Huang).
1438-4639/$ - see front matter r 2008 Elsevier GmbH. All rights reserved. doi:10.1016/j.ijheh.2008.01.002
symptom is usually difficulty in convergence of the eyes, followed by ptosis and paralysis of the extraocular muscles. The pupils become dilated and may not react to light. These symptoms often progress to weakness of jaw muscles, dysphagia, and dysarthria. Autonomic symptoms such as dry mouth, constipation and urine retention have also been reported. Botulism is a rare disease. In the United States, there are about 100 to 110 cases per year of botulism (Shapiro et al., 1998). In Taiwan, an outbreak of type A botulism caused by contaminated canned food was reported in 1986 and an outbreak of type B botulism caused by fermented food was reported in 1990 (Table 1); only a few sporadic cases have been reported since then. Because of the rarity of botulism in Taiwan, many physicians are unfamiliar with its clinical manifestations; therefore, the disease is probably underdiagnosed
ARTICLE IN PRESS C.-K. Tseng et al. / Int. J. Hyg. Environ. Health 212 (2009) 82–86
Table 1.
83
Characteristics of patients with botulism in Taiwan, 1985–2006
Case no.
Vehicles
Symptom type
Laboratory confirm
1986 7 1
Canned food Fermented food
CN GI
Type A toxin in food specimen Type B toxin in serum specimen
An outbreak of type A botulism A sporadic case
1987 1
?
GI
1
?
GI, CN
Type B toxin in serum and stool specimen Type A toxin in stool specimen
First case reported of infantile botulism in Taiwan A sporadic case
Fermented food Fermented food
GI
Type B toxin in serum specimen
An outbreak of type B botulism
GI, CN
Type B toxin in food specimen
An outbreak of type B botulism
1990 11 2006 5
Note: CN, cranial nerve (i.e., ptosis, blurred vision, diplopia); GI, gastrointestinal (i.e., dysphagia, ileus).
(Merz et al., 2003). We report an outbreak of type B botulism in Taiwan in 2006 and demonstrate the importance of rapid diagnoses.
Narrative On 29 May 2006, a 56-year-old man with a history of hypertension was transferred to our emergency department (ED) from a local hospital. The patient presented with a 3-day history of blurred vision, ptosis, dilated pupils, ophthalmoplegia, dysphagia, constipation and urine retention. The preliminary diagnosis was Miller– Fisher syndrome. Over the next 18 h, the loss of cranial nerve function was almost complete. The patient gradually developed descending paralysis which ultimately resulted in respiratory paralysis at noon the day after admission, although his consciousness remained clear, his muscle strength was 4/5 in all extremities and sensation was intact. The patient was intubated and mechanically ventilated. He was transferred to the neurology intensive care unit (ICU). The patient’s blood count, biochemical profile, computerized tomography and magnetic resonance images of the head were all normal. The patient did not require sedative medication. A preliminary clinical diagnosis of botulism was made, and the Center for Disease Control and Prevention (CDC, Taiwan) was contacted to determine the extent of the outbreak, to identify the source of the contaminated food, and to enact control measures. According to the family’s statement, the patient’s blood pressure was normally 130/90 mmHg under antihypertensive control. However, in our ICU, his blood pressure had fallen to 110/ 70 mmHg without antihypertensive control. Furthermore, ileus persisted and no stool sample could be collected after admission. Stool softeners and stimulant
laxatives were administered but in vain. Hyperosmotic laxatives were administered on the 12th day after admission and massive stool passage was noted. Administration of hyperosmotic laxatives was maintained; 3 days later, the patient’s light reflex returned to normal and the ptosis improved. Samples of blood, stool and food were sent to the CDC, Taiwan, to be cultured for the presence of C. botulinum and its toxin; approximately 20 days later, the CDC reported that the food was positive for botulinum toxin B. The patient’s neuromuscular function gradually improved under supportive treatment and the endotracheal tube was removed on the 24th day of hospitalization. The patient was discharged home on the 41st admission day after completing an aggressive rehabilitation program. Initially, the patient and his family members all denied having eaten any contaminated food. Finally, they recalled that the patient had trapped and killed a wild goat about 3 weeks before visiting our ED. The patient had preserved the raw goat meat with boiled rice in a jug. The dish is called Cinkrugan and is a traditional recipe of the Atalya tribe to which the man belonged. The raw goat meat is allowed to ferment for about 1 week. When Cinkrugan is ready for consumption, the meat normally has a whitish hue; however, on this occasion, the meat was an unusually dark green color. A total of five people in this family consumed the raw goat meat and we labeled these patients from A to E. All of them reported having had similar symptoms after eating the meat, such as dry mouth, blurred vision, ileus and hiccup. Patient A was the one who had been admitted to our ICU; he had eaten the largest amount of the contaminated meat and presented with the most serious symptoms (Table 2). Patients D and E said that they had only taken one or two bites of the meat and reported having experienced only mild symptoms, which resolved within 1 day. In addition to the above symptoms, patient C also suffered from dyspnea while exercising
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Table 2. Clinical manifestations of the five patients with foodborne botulism in Taiwan in 2006 Symptom
Ptosis Dry mouth Dysphagia Blurred vision Diplopia Limbs weakness Dyspnea Nausea Vomiting Hiccup Epigastralgia Ileus Diarrhea Urine retention Hypotension
Patient A
B
C
D
E
+ + + + +
+ + +
+ + +
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ +
+
Note: Patient A revealed the most serious symptoms because he ingested the largest amount of contaminated meat. Patients D and E did not require medical help because they had ingested only a small amount of the contaminated meat and presented with only mild symptoms. The gray rows mean the common symptoms of all patients.
and dysphagia. He visited the infirmary of a military hospital for help where a slight drop in blood pressure was noted. He was admitted with supportive treatment and discharged 5 days later after the symptoms subsided. Patient B presented dysphagia and ileus in our Gastroenterology clinic. She was admitted to the gastroenterology ward and esophagogastroduodenoscopy was scheduled. She was then referred to neurology ward in the second day of admission after the informing of Neurologist. She was discharged 10 days later after symptoms improved.
Discussion Botulinum toxin is one of the most poisonous naturally occurring substances in the world (Gill, 1982). It is easily disseminated and transmitted and causes high mortality rates. Botulism is therefore classified as a category A substance on the CDC’s list of critical biological agents (Prevention CfDCa, 2000). C. botulinum is classified into seven types according to the antigens of the neurotoxins (referred to as A–G types). Types A, B, E and F cause disease in humans. Types C and D cause botulism in birds and mammals but have not caused botulism in humans. Type G toxin was identified in 1970 but has never been reported to have caused botulism in animals or humans. There are four manifestations of botulism. Ingestion of food
contaminated with C. botulinum may cause foodborne botulism (Aureli et al., 2000). Infantile botulism is the most frequently manifested form of botulism in the United States. It occurs with the ingestion of C. botulinum spores. Because of the lack of protective flora in the immature intestinal tract, the C. botulinum spores colonize and produce toxin (Arnon et al., 1979). Infant-like botulism often occurs in patients with gastrointestinal abnormality or recent antibiotics use. Wound botulism may occur in wounds after contamination with C. botulinum (Chia et al., 1986). No cases of waterborne botulism have ever been reported (Gangarosa et al., 1971). In fact, waterborne botulism is unlikely in standard portable water treatments because of two reasons. One is that the activation of botulinum toxin will be rapidly destroyed after chlorination and aeration. The other is that large amounts of botulinum toxin will be needed in a large-capacity reservoir. It is technically difficult in production and delivery. In Asia, foodborne botulism is an important entity because of the popularity of fermented food. In Japan, there were 86 cases of foodborne botulism reported during 1955 through 1998 (Infectious Disease Surveillance Center, 2000). In China, there were 4377 cases of botulism involved in 986 outbreaks during 1958–1983. Homemade fermented bean curd accounted for the majority (74%) of these outbreaks (Shih and Chao, 1986). The diagnosis of botulism should be based on the patient’s initial symptoms and history. However, botulism is often not considered to be a differential diagnosis because of its rarity. Some sporadic cases may be missed entirely (Horwitz et al., 1975; Koenig et al., 1964). Botulism should be suspected if a patient simultaneously reveals acute onset of autonomic, cranial nerve and gastrointestinal dysfunction. The associated autonomic dysfunction includes urinary retention, dry mouth and hypotension. Cranial nerve dysfunction includes diplopia, dysphagia and ptosis. The gastrointestinal problems include nausea, vomiting and paralytic ileus (Armada et al., 2003; Lund, 1990). Fever and the abnormality of serum study are not expected in a patient with botulism unless secondary infection occurs. The diagnosis of botulism can be confirmed after collecting samples of food, serum and stool. In Taiwan, testing is performed by the CDC, Taiwan. Associated diagnostic tests include stool and food culture, and serous toxin type identification by the mouse inoculation test (Aureli et al., 2000; Kalluri et al., 2003). Unfortunately, these testing procedures take many days to complete. Earlier sample collecting will increase the sensitivity of these tests. According to a review article, the serum toxin isolation rate will decrease to 30% from 35% after more than 2 days of ingestion (Cherington, 1998). A study by Woodruff revealed that the positive rate of serous toxin is only 13–28% after 2 days of ingestion (Woodruff
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et al., 1992). The positive rate of stool culture will decrease to 36% after 3 days (Cherington, 1998). In the very early stage of botulism, antitoxin therapy is suggested. Botulinum antitoxin is the only specific therapy for botulism. It can neutralize the free toxin molecules in the serum and prevent them from biding to nerve endings. Some studies have revealed that earlier antitoxin administration will result in better outcome (Chang and Ganguly, 2003; Sandrock and Murin, 2001; Shapiro et al., 1997; Tacket et al., 1984). Botulinum antitoxin is an equine product containing antibodies to types A, B and E toxins. The antitoxin binds only to free circulating toxin; once the toxin binds to the presynaptic nerve endings, the process is irreversible. Serious side-effects occur in 9% of patients (Black and Gunn, 1980). The function recovery requires the growth of new terminals and the formation of new synapses (Shapiro et al., 1998). After the early stage of botulism, supportive treatment and complication prevention is the main goal of clinical care. Patients with severe forms of botulism accompanied with respiratory failure often need ventilator support and intensive care. The duration of recovery from respiratory failure will be weeks, if not months. Medical resources would be exhausted if many people were simultaneously infected, as would be the case in an intended distribution. The use of laxatives and cathartics in the treatment of foodborne botulism is still controversial. In our opinion, removing the contents of the gastrointestinal tract that may still contain C. botulinum will block the absorption of botulinum toxin. In our case, the recovery of light reflex and the improvement of ptosis in patient A occurred 3 days after massive stool passage. Although the patient’s recovery could have been due to the nature course of the disease, it is also may have been due to the effect of stool and Botulinum passage. Furthermore, in our experience, the effect of hyperosmotic laxatives is much better than the effect of stool softeners and stimulant laxatives for patients with paralytic ileus. In conclusion, we present an outbreak of type B botulism in Taiwan. The diagnosis was based on the patient’s rapid deterioration and presentation of descending paralysis, several members of one household were affected and as well as positive culture of the contaminated food. We suppose that the course of the illness depends on the amount of toxin absorbed from the gut. Treatment of botulism includes early administration of antitoxin and supportive care. If suspected, botulinum antitoxin should be given, particularly within the first 24 h of symptom onset while the toxin is still in the blood. Confirmation of the presence of botulinum usually takes time. The most reliable method for identification of C. botulinum toxin is mouse inoculation test and the mouse bioassay requires approximately 4 days for final results. The death rate associated with type B botulism is 10% (Austin and Dodds, 1996). With
85
critical care management, the death rate of all types of botulism is 14% (Austin and Dodds, 1996). Respiratory failure has been a major cause of morbidity and mortality of the disease. Patients who did not receive antitoxin within 12 h after presentation were three times more likely to develop respiratory failure in 20 patients with wound botulism after black tar heroin consumption (Sandrock and Murin, 2001). Therefore, early diagnosis and management rely on history and physical examination.
References Armada, M., Love, S., Barrett, E., Monroe, J., Peery, D., Sobel, J., 2003. Foodborne botulism in a six-month-old infant caused by home-canned baby food. Ann. Emerg. Med. 42, 226–229. Arnon, S.S., Midura, T.F., Damus, K., Thompson, B., Wood, R.M., Chin, J., 1979. Honey and other environmental risk factors for infant botulism. J. Pediatr. 94, 331–336. Aureli, P., Di Cunto, M., Maffei, A., De Chiara, G., Franciosa, G., Accorinti, L., Gambardella, A.M., Greco, D., 2000. An outbreak in Italy of botulism associated with a dessert made with mascarpone cream cheese. Eur. J. Epidemiol. 16, 913–918. Austin, J., Dodds, K., 1996. Botulism reference service for Canada. Can. Commun. Dis. Rep. 22, 183–184. Black, R.E., Gunn, R.A., 1980. Hypersensitivity reactions associated with botulinal antitoxin. Am. J. Med. 69, 567–570. Chang, G.Y., Ganguly, G., 2003. Early antitoxin treatment in wound botulism results in better outcome. Eur. Neurol. 49, 151–153. Cherington, M., 1998. Clinical spectrum of botulism. Muscle Nerve 21, 701–710. Chia, J.K., Clark, J.B., Ryan, C.A., Pollack, M., 1986. Botulism in an adult associated with food-borne intestinal infection with Clostridium botulinum. N. Engl. J. Med. 315, 239–241. Gangarosa, E.J., Donadio, J.A., Armstrong, R.W., Meyer, K.F., Brachman, P.S., Dowell, V.R., 1971. Botulism in the United States, 1899–1969. Am. J. Epidemiol. 93, 93–101. Gill, D.M., 1982. Bacterial toxins: a table of lethal amounts. Microbiol. Rev. 46, 86–94. Horwitz, M.A., Marr, J.S., Merson, M.H., Dowell, V.R., Ellis, J.M., 1975. A continuing common-source outbreak of botulism in a family. Lancet 2, 861–863. Infectious Disease Surveillance Center J, 2000. Botulism, Japan. In: IASR. Infectious Disease Surveillance Center. Kalluri, P., Crowe, C., Reller, M., Gaul, L., Hayslett, J., Barth, S., Eliasberg, S., Ferreira, J., Holt, K., Bengston, S., Hendricks, K., Sobel, J., 2003. An outbreak of foodborne botulism associated with food sold at a salvage store in Texas. Clin. Infect. Dis. 37, 1490–1495. Koenig, M.G., Spickard, A., Cardella, M.A., Rogers, D.E., 1964. Clinical and laboratory observations on type E Botulism in man. Medicine (Baltimore) 43, 517–545. Lund, B.M., 1990. Foodborne disease due to Bacillus and Clostridium species. Lancet 336, 982–986. Mackle, I.J., Halcomb, E., Parr, M.J., 2001. Severe adult botulism. Anaesth. Intensive Care 29, 297–300.
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Merz, B., Bigalke, H., Stoll, G., Naumann, M., 2003. Botulism type B presenting as pure autonomic dysfunction. Clin. Auton. Res. 13, 337–338. Prevention CfDCa, 2000. Biological and chemical terrorism: strategic plan for preparedness and response. Recommendations of the CDC Strategic Planning Workgroup MMWR Recommendation Report 49 (RR-4), 1–148. Sandrock, C.E., Murin, S., 2001. Clinical predictors of respiratory failure and long-term outcome in black tar heroin-associated wound botulism. Chest 120, 562–566. Shapiro, R.L., Hatheway, C., Becher, J., Swerdlow, D.L., 1997. Botulism surveillance and emergency response. A public health strategy for a global challenge. JAMA 278, 433–435.
Shapiro, R.L., Hatheway, C., Swerdlow, D.L., 1998. Botulism in the United States: a clinical and epidemiologic review. Ann. Intern. Med. 129, 221–228. Shih, Y., Chao, S.Y., 1986. Botulism in China. Rev. Infect. Dis. 8, 984–990. Tacket, C.O., Shandera, W.X., Mann, J.M., Hargrett, N.T., Blake, P.A., 1984. Equine antitoxin use and other factors that predict outcome in type A foodborne botulism. Am. J. Med. 76, 794–798. Woodruff, B.A., Griffin, P.M., McCroskey, L.M., Smart, J.F., Wainwright, R.B., Bryant, R.G., Hutwagner, L.C., Hatheway, C.L., 1992. Clinical and laboratory comparison of botulism from toxin types A, B, and E in the United States, 1975–1988. J. Infect. Dis. 166, 1281–1286.
Int. J. Hyg. Environ. Health 212 (2009) 82–86 www.elsevier.de/ijheh
An outbreak of foodborne botulism in Taiwan Chun-Kai Tsenga, Chon-Haw Tsaib, Chun-Hung Tsengb, Yu-Chi Tsenga, Fang-Yi Leec, Wei-Shih Huangb, a
Department of Emergency Medicine, China Medical University Hospital, Taichung, Taiwan Department of Neurology, China Medical University Hospital, Taichung, Taiwan c Department of Pathology, Taichung Veterans General Hospital, Taichung, Taiwan b
Received 6 June 2007; received in revised form 2 January 2008; accepted 23 January 2008
Abstract Botulism is a rare but serious paralytic disease caused by botulinum toxin. We report an outbreak of type B botulism in Taiwan in 2006. There were five cases involved in this outbreak. They present ileus and acute cranial nerve dysfunction including dysphagia and blurred vision. One of them had severe neurologic impairment and required mechanical ventilatory support. No patient received antitoxin administration because of delayed diagnosis. The food specimen revealed positive botulism toxin B. There were no fatalities. Consumption of fermented food was significantly associated with this outbreak. We also reviewed the characteristics of cases with botulism in Taiwan since 1985. r 2008 Elsevier GmbH. All rights reserved. Keywords: Antitoxin; Clostridium botulinum; Foodborne botulism; Type B
Introduction Clostridium botulinum is an anaerobic, gram-positive, spore-forming bacillus which exists in soil worldwide (Lund, 1990). It produces neurotoxins which bind to the pre-synaptic nerve endings of peripheral cholinergic nerves after entering the vascular system. The binding between botulinum toxin and peripheral cholinergic nerve endings blocks the release of acetylcholine which induces weakness of the innervating muscles. Associated symptoms include neurological, autonomic and gastrointestinal symptoms (Mackle et al., 2001). The initial Corresponding author. Tel.: +886 4 2052121x3681; fax: +886 4 22033474. E-mail addresses: [email protected], [email protected] (W.-S. Huang).
1438-4639/$ - see front matter r 2008 Elsevier GmbH. All rights reserved. doi:10.1016/j.ijheh.2008.01.002
symptom is usually difficulty in convergence of the eyes, followed by ptosis and paralysis of the extraocular muscles. The pupils become dilated and may not react to light. These symptoms often progress to weakness of jaw muscles, dysphagia, and dysarthria. Autonomic symptoms such as dry mouth, constipation and urine retention have also been reported. Botulism is a rare disease. In the United States, there are about 100 to 110 cases per year of botulism (Shapiro et al., 1998). In Taiwan, an outbreak of type A botulism caused by contaminated canned food was reported in 1986 and an outbreak of type B botulism caused by fermented food was reported in 1990 (Table 1); only a few sporadic cases have been reported since then. Because of the rarity of botulism in Taiwan, many physicians are unfamiliar with its clinical manifestations; therefore, the disease is probably underdiagnosed
ARTICLE IN PRESS C.-K. Tseng et al. / Int. J. Hyg. Environ. Health 212 (2009) 82–86
Table 1.
83
Characteristics of patients with botulism in Taiwan, 1985–2006
Case no.
Vehicles
Symptom type
Laboratory confirm
1986 7 1
Canned food Fermented food
CN GI
Type A toxin in food specimen Type B toxin in serum specimen
An outbreak of type A botulism A sporadic case
1987 1
?
GI
1
?
GI, CN
Type B toxin in serum and stool specimen Type A toxin in stool specimen
First case reported of infantile botulism in Taiwan A sporadic case
Fermented food Fermented food
GI
Type B toxin in serum specimen
An outbreak of type B botulism
GI, CN
Type B toxin in food specimen
An outbreak of type B botulism
1990 11 2006 5
Note: CN, cranial nerve (i.e., ptosis, blurred vision, diplopia); GI, gastrointestinal (i.e., dysphagia, ileus).
(Merz et al., 2003). We report an outbreak of type B botulism in Taiwan in 2006 and demonstrate the importance of rapid diagnoses.
Narrative On 29 May 2006, a 56-year-old man with a history of hypertension was transferred to our emergency department (ED) from a local hospital. The patient presented with a 3-day history of blurred vision, ptosis, dilated pupils, ophthalmoplegia, dysphagia, constipation and urine retention. The preliminary diagnosis was Miller– Fisher syndrome. Over the next 18 h, the loss of cranial nerve function was almost complete. The patient gradually developed descending paralysis which ultimately resulted in respiratory paralysis at noon the day after admission, although his consciousness remained clear, his muscle strength was 4/5 in all extremities and sensation was intact. The patient was intubated and mechanically ventilated. He was transferred to the neurology intensive care unit (ICU). The patient’s blood count, biochemical profile, computerized tomography and magnetic resonance images of the head were all normal. The patient did not require sedative medication. A preliminary clinical diagnosis of botulism was made, and the Center for Disease Control and Prevention (CDC, Taiwan) was contacted to determine the extent of the outbreak, to identify the source of the contaminated food, and to enact control measures. According to the family’s statement, the patient’s blood pressure was normally 130/90 mmHg under antihypertensive control. However, in our ICU, his blood pressure had fallen to 110/ 70 mmHg without antihypertensive control. Furthermore, ileus persisted and no stool sample could be collected after admission. Stool softeners and stimulant
laxatives were administered but in vain. Hyperosmotic laxatives were administered on the 12th day after admission and massive stool passage was noted. Administration of hyperosmotic laxatives was maintained; 3 days later, the patient’s light reflex returned to normal and the ptosis improved. Samples of blood, stool and food were sent to the CDC, Taiwan, to be cultured for the presence of C. botulinum and its toxin; approximately 20 days later, the CDC reported that the food was positive for botulinum toxin B. The patient’s neuromuscular function gradually improved under supportive treatment and the endotracheal tube was removed on the 24th day of hospitalization. The patient was discharged home on the 41st admission day after completing an aggressive rehabilitation program. Initially, the patient and his family members all denied having eaten any contaminated food. Finally, they recalled that the patient had trapped and killed a wild goat about 3 weeks before visiting our ED. The patient had preserved the raw goat meat with boiled rice in a jug. The dish is called Cinkrugan and is a traditional recipe of the Atalya tribe to which the man belonged. The raw goat meat is allowed to ferment for about 1 week. When Cinkrugan is ready for consumption, the meat normally has a whitish hue; however, on this occasion, the meat was an unusually dark green color. A total of five people in this family consumed the raw goat meat and we labeled these patients from A to E. All of them reported having had similar symptoms after eating the meat, such as dry mouth, blurred vision, ileus and hiccup. Patient A was the one who had been admitted to our ICU; he had eaten the largest amount of the contaminated meat and presented with the most serious symptoms (Table 2). Patients D and E said that they had only taken one or two bites of the meat and reported having experienced only mild symptoms, which resolved within 1 day. In addition to the above symptoms, patient C also suffered from dyspnea while exercising
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Table 2. Clinical manifestations of the five patients with foodborne botulism in Taiwan in 2006 Symptom
Ptosis Dry mouth Dysphagia Blurred vision Diplopia Limbs weakness Dyspnea Nausea Vomiting Hiccup Epigastralgia Ileus Diarrhea Urine retention Hypotension
Patient A
B
C
D
E
+ + + + +
+ + +
+ + +
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ +
+
Note: Patient A revealed the most serious symptoms because he ingested the largest amount of contaminated meat. Patients D and E did not require medical help because they had ingested only a small amount of the contaminated meat and presented with only mild symptoms. The gray rows mean the common symptoms of all patients.
and dysphagia. He visited the infirmary of a military hospital for help where a slight drop in blood pressure was noted. He was admitted with supportive treatment and discharged 5 days later after the symptoms subsided. Patient B presented dysphagia and ileus in our Gastroenterology clinic. She was admitted to the gastroenterology ward and esophagogastroduodenoscopy was scheduled. She was then referred to neurology ward in the second day of admission after the informing of Neurologist. She was discharged 10 days later after symptoms improved.
Discussion Botulinum toxin is one of the most poisonous naturally occurring substances in the world (Gill, 1982). It is easily disseminated and transmitted and causes high mortality rates. Botulism is therefore classified as a category A substance on the CDC’s list of critical biological agents (Prevention CfDCa, 2000). C. botulinum is classified into seven types according to the antigens of the neurotoxins (referred to as A–G types). Types A, B, E and F cause disease in humans. Types C and D cause botulism in birds and mammals but have not caused botulism in humans. Type G toxin was identified in 1970 but has never been reported to have caused botulism in animals or humans. There are four manifestations of botulism. Ingestion of food
contaminated with C. botulinum may cause foodborne botulism (Aureli et al., 2000). Infantile botulism is the most frequently manifested form of botulism in the United States. It occurs with the ingestion of C. botulinum spores. Because of the lack of protective flora in the immature intestinal tract, the C. botulinum spores colonize and produce toxin (Arnon et al., 1979). Infant-like botulism often occurs in patients with gastrointestinal abnormality or recent antibiotics use. Wound botulism may occur in wounds after contamination with C. botulinum (Chia et al., 1986). No cases of waterborne botulism have ever been reported (Gangarosa et al., 1971). In fact, waterborne botulism is unlikely in standard portable water treatments because of two reasons. One is that the activation of botulinum toxin will be rapidly destroyed after chlorination and aeration. The other is that large amounts of botulinum toxin will be needed in a large-capacity reservoir. It is technically difficult in production and delivery. In Asia, foodborne botulism is an important entity because of the popularity of fermented food. In Japan, there were 86 cases of foodborne botulism reported during 1955 through 1998 (Infectious Disease Surveillance Center, 2000). In China, there were 4377 cases of botulism involved in 986 outbreaks during 1958–1983. Homemade fermented bean curd accounted for the majority (74%) of these outbreaks (Shih and Chao, 1986). The diagnosis of botulism should be based on the patient’s initial symptoms and history. However, botulism is often not considered to be a differential diagnosis because of its rarity. Some sporadic cases may be missed entirely (Horwitz et al., 1975; Koenig et al., 1964). Botulism should be suspected if a patient simultaneously reveals acute onset of autonomic, cranial nerve and gastrointestinal dysfunction. The associated autonomic dysfunction includes urinary retention, dry mouth and hypotension. Cranial nerve dysfunction includes diplopia, dysphagia and ptosis. The gastrointestinal problems include nausea, vomiting and paralytic ileus (Armada et al., 2003; Lund, 1990). Fever and the abnormality of serum study are not expected in a patient with botulism unless secondary infection occurs. The diagnosis of botulism can be confirmed after collecting samples of food, serum and stool. In Taiwan, testing is performed by the CDC, Taiwan. Associated diagnostic tests include stool and food culture, and serous toxin type identification by the mouse inoculation test (Aureli et al., 2000; Kalluri et al., 2003). Unfortunately, these testing procedures take many days to complete. Earlier sample collecting will increase the sensitivity of these tests. According to a review article, the serum toxin isolation rate will decrease to 30% from 35% after more than 2 days of ingestion (Cherington, 1998). A study by Woodruff revealed that the positive rate of serous toxin is only 13–28% after 2 days of ingestion (Woodruff
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et al., 1992). The positive rate of stool culture will decrease to 36% after 3 days (Cherington, 1998). In the very early stage of botulism, antitoxin therapy is suggested. Botulinum antitoxin is the only specific therapy for botulism. It can neutralize the free toxin molecules in the serum and prevent them from biding to nerve endings. Some studies have revealed that earlier antitoxin administration will result in better outcome (Chang and Ganguly, 2003; Sandrock and Murin, 2001; Shapiro et al., 1997; Tacket et al., 1984). Botulinum antitoxin is an equine product containing antibodies to types A, B and E toxins. The antitoxin binds only to free circulating toxin; once the toxin binds to the presynaptic nerve endings, the process is irreversible. Serious side-effects occur in 9% of patients (Black and Gunn, 1980). The function recovery requires the growth of new terminals and the formation of new synapses (Shapiro et al., 1998). After the early stage of botulism, supportive treatment and complication prevention is the main goal of clinical care. Patients with severe forms of botulism accompanied with respiratory failure often need ventilator support and intensive care. The duration of recovery from respiratory failure will be weeks, if not months. Medical resources would be exhausted if many people were simultaneously infected, as would be the case in an intended distribution. The use of laxatives and cathartics in the treatment of foodborne botulism is still controversial. In our opinion, removing the contents of the gastrointestinal tract that may still contain C. botulinum will block the absorption of botulinum toxin. In our case, the recovery of light reflex and the improvement of ptosis in patient A occurred 3 days after massive stool passage. Although the patient’s recovery could have been due to the nature course of the disease, it is also may have been due to the effect of stool and Botulinum passage. Furthermore, in our experience, the effect of hyperosmotic laxatives is much better than the effect of stool softeners and stimulant laxatives for patients with paralytic ileus. In conclusion, we present an outbreak of type B botulism in Taiwan. The diagnosis was based on the patient’s rapid deterioration and presentation of descending paralysis, several members of one household were affected and as well as positive culture of the contaminated food. We suppose that the course of the illness depends on the amount of toxin absorbed from the gut. Treatment of botulism includes early administration of antitoxin and supportive care. If suspected, botulinum antitoxin should be given, particularly within the first 24 h of symptom onset while the toxin is still in the blood. Confirmation of the presence of botulinum usually takes time. The most reliable method for identification of C. botulinum toxin is mouse inoculation test and the mouse bioassay requires approximately 4 days for final results. The death rate associated with type B botulism is 10% (Austin and Dodds, 1996). With
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critical care management, the death rate of all types of botulism is 14% (Austin and Dodds, 1996). Respiratory failure has been a major cause of morbidity and mortality of the disease. Patients who did not receive antitoxin within 12 h after presentation were three times more likely to develop respiratory failure in 20 patients with wound botulism after black tar heroin consumption (Sandrock and Murin, 2001). Therefore, early diagnosis and management rely on history and physical examination.
References Armada, M., Love, S., Barrett, E., Monroe, J., Peery, D., Sobel, J., 2003. Foodborne botulism in a six-month-old infant caused by home-canned baby food. Ann. Emerg. Med. 42, 226–229. Arnon, S.S., Midura, T.F., Damus, K., Thompson, B., Wood, R.M., Chin, J., 1979. Honey and other environmental risk factors for infant botulism. J. Pediatr. 94, 331–336. Aureli, P., Di Cunto, M., Maffei, A., De Chiara, G., Franciosa, G., Accorinti, L., Gambardella, A.M., Greco, D., 2000. An outbreak in Italy of botulism associated with a dessert made with mascarpone cream cheese. Eur. J. Epidemiol. 16, 913–918. Austin, J., Dodds, K., 1996. Botulism reference service for Canada. Can. Commun. Dis. Rep. 22, 183–184. Black, R.E., Gunn, R.A., 1980. Hypersensitivity reactions associated with botulinal antitoxin. Am. J. Med. 69, 567–570. Chang, G.Y., Ganguly, G., 2003. Early antitoxin treatment in wound botulism results in better outcome. Eur. Neurol. 49, 151–153. Cherington, M., 1998. Clinical spectrum of botulism. Muscle Nerve 21, 701–710. Chia, J.K., Clark, J.B., Ryan, C.A., Pollack, M., 1986. Botulism in an adult associated with food-borne intestinal infection with Clostridium botulinum. N. Engl. J. Med. 315, 239–241. Gangarosa, E.J., Donadio, J.A., Armstrong, R.W., Meyer, K.F., Brachman, P.S., Dowell, V.R., 1971. Botulism in the United States, 1899–1969. Am. J. Epidemiol. 93, 93–101. Gill, D.M., 1982. Bacterial toxins: a table of lethal amounts. Microbiol. Rev. 46, 86–94. Horwitz, M.A., Marr, J.S., Merson, M.H., Dowell, V.R., Ellis, J.M., 1975. A continuing common-source outbreak of botulism in a family. Lancet 2, 861–863. Infectious Disease Surveillance Center J, 2000. Botulism, Japan. In: IASR. Infectious Disease Surveillance Center. Kalluri, P., Crowe, C., Reller, M., Gaul, L., Hayslett, J., Barth, S., Eliasberg, S., Ferreira, J., Holt, K., Bengston, S., Hendricks, K., Sobel, J., 2003. An outbreak of foodborne botulism associated with food sold at a salvage store in Texas. Clin. Infect. Dis. 37, 1490–1495. Koenig, M.G., Spickard, A., Cardella, M.A., Rogers, D.E., 1964. Clinical and laboratory observations on type E Botulism in man. Medicine (Baltimore) 43, 517–545. Lund, B.M., 1990. Foodborne disease due to Bacillus and Clostridium species. Lancet 336, 982–986. Mackle, I.J., Halcomb, E., Parr, M.J., 2001. Severe adult botulism. Anaesth. Intensive Care 29, 297–300.
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Merz, B., Bigalke, H., Stoll, G., Naumann, M., 2003. Botulism type B presenting as pure autonomic dysfunction. Clin. Auton. Res. 13, 337–338. Prevention CfDCa, 2000. Biological and chemical terrorism: strategic plan for preparedness and response. Recommendations of the CDC Strategic Planning Workgroup MMWR Recommendation Report 49 (RR-4), 1–148. Sandrock, C.E., Murin, S., 2001. Clinical predictors of respiratory failure and long-term outcome in black tar heroin-associated wound botulism. Chest 120, 562–566. Shapiro, R.L., Hatheway, C., Becher, J., Swerdlow, D.L., 1997. Botulism surveillance and emergency response. A public health strategy for a global challenge. JAMA 278, 433–435.
Shapiro, R.L., Hatheway, C., Swerdlow, D.L., 1998. Botulism in the United States: a clinical and epidemiologic review. Ann. Intern. Med. 129, 221–228. Shih, Y., Chao, S.Y., 1986. Botulism in China. Rev. Infect. Dis. 8, 984–990. Tacket, C.O., Shandera, W.X., Mann, J.M., Hargrett, N.T., Blake, P.A., 1984. Equine antitoxin use and other factors that predict outcome in type A foodborne botulism. Am. J. Med. 76, 794–798. Woodruff, B.A., Griffin, P.M., McCroskey, L.M., Smart, J.F., Wainwright, R.B., Bryant, R.G., Hutwagner, L.C., Hatheway, C.L., 1992. Clinical and laboratory comparison of botulism from toxin types A, B, and E in the United States, 1975–1988. J. Infect. Dis. 166, 1281–1286.